Dataset Information

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio).

ABSTRACT: Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in ?-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated transcription factor (Mitf) and the other downstream melanogenic-related genes were verified via quantitative real time PCR (qPCR). Toxicity assessment and melanogenesis inhibition on zebrafish model was further observed. FLA and FLB significantly reduced the specific cellular melanin content by 4.3-fold and 9.6-fold decrement, respectively in ?-MSH-induced B16/F10 cells. Concomitantly, FLA significantly reduced the specific cellular tyrosinase activity by 7-fold whilst FLB by 9-fold. The decrement of melanin production and tyrosinase activity were correlated with the mRNA suppression of Mitf which in turn down-regulate Tyr, Trp-1 and Trp-2. FLA and FLB exhibited non-toxic effects on the zebrafish model at 25 and 6.25 µM, respectively. Further experiments on the zebrafish model demonstrated successful phenotype-based depigmenting activity of FLA and FLB under induced melanogenesis. To sum up, our findings provide an important first key step for both of the chalcone derivatives to be further studied and developed as potent depigmenting agents.

SUBMITTER: Mohd Sakeh N

PROVIDER: S-EPMC7436045 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (<i>Danio rerio</i>).

Mohd Sakeh Nurshafika N Md Razip Nurliyana Najwa NN Mohd Ma'in Farah Idayu FI Abdul Bahari Mohammad Nazri MN Latif Naimah N Akhtar Muhammad Nadeem MN Balia Yusof Zetty Norhana ZN Ahmad Syahida S

Molecules (Basel, Switzerland) 20200728 15

Excessive production of melanin implicates hyperpigmentation disorders. Flavokawain A (FLA) and flavokawain B (FLB) have been reported with anti-melanogenic activity, but their melanogenic inhibition and toxicity effects on the vertebrate model of zebrafish are still unknown. In the present study, cytotoxic as well as melanogenic effects of FLA and FLB on cellular melanin content and tyrosinase activity were evaluated in α-MSH-induced B16/F10 cells. Master regulator of microphthalmia-associated ...[more]

PMID: 32731323

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Project description:Dysregulation of microRNA (miRNA, miR) by environmental stressors influences the transcription of mRNA which may impair organism development and/or lead to adverse physiological outcomes. Early studies evaluating the effects of oil on developmental toxicity in early life stages of fish showed that reductions in expression of miR-203a were associated with enhanced expression of downstream mRNAs that predicted altered eye development, cardiovascular disease, and improper fin development. To better understand the effects of miR-203a inhibition as an outcome of oil-induced toxicity in early life stage (ELS) fish, embryonic zebrafish were injected with an miR-203a inhibitor or treated with 3.5 µM phenanthrene (Phe) as a positive control for morphological alterations of cardiovascular and eye development caused by oil. Embryos treated with Phe had diminished levels of miR-203a at 7 and 72 h after injection. Embryos treated with the miR-203a inhibitor and Phe exhibited a reduced heart rate by 48 h post fertilization (hpf), with an increased incidence of developmental deformities (including pericardial edema, altered eye development, and spinal deformities) and reduced caudal fin length by 72 hpf. There were significant reductions in lens and eye diameters in 120 hpf miR-203a-inhibitor and Phe-treated fish, as well as a significantly reduced number of eye saccades, determined by an optokinetic response (OKR) behavioral assay. The expression of vegfa, which is an important activator during neovascularization, was significantly upregulated in embryos receiving miR-203a inhibitor injections by 7 and 72 hpf with increased trends in vegfa expression in 72 hpf larvae treated with Phe. There were decreasing trends in crx, neurod1, and pde6h expression by 72 hpf in miR-203a inhibitor and Phe treatments, which are involved in photoreceptor function in developing eyes and regulated by miR-203a. These results suggest that an inhibition of miR-203a in ELS fish exhibits an oil-induced toxic response that is consistent with Phe treatment and specifically impacts retinal, cardiac, and fin development in ELS fish.

Dataset Information

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (Danio rerio).

Publications

Melanogenic Inhibition and Toxicity Assessment of Flavokawain A and B on B16/F10 Melanoma Cells and Zebrafish (<i>Danio rerio</i>).

Similar Datasets

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